@article{68ab8d36bacc49bbb17ce08736171b5e,
title = "Glucose promotes cell growth by suppressing branched-chain amino acid degradation",
abstract = "Glucose and branched-chain amino acids (BCAAs) are essential nutrients and key determinants of cell growth and stress responses. High BCAA level inhibits glucose metabolism but reciprocal regulation of BCAA metabolism by glucose has not been demonstrated. Here we show that glucose suppresses BCAA catabolism in cardiomyocytes to promote hypertrophic response. High glucose inhibits CREB stimulated KLF15 transcription resulting in downregulation of enzymes in the BCAA catabolism pathway. Accumulation of BCAA through the glucose-KLF15-BCAA degradation axis is required for the activation of mTOR signaling during the hypertrophic growth of cardiomyocytes. Restoration of KLF15 prevents cardiac hypertrophy in response to pressure overload in wildtype mice but not in mutant mice deficient of BCAA degradation gene. Thus, regulation of KLF15 transcription by glucose is critical for the glucose-BCAA circuit which controls a cascade of obligatory metabolic responses previously unrecognized for cell growth.",
author = "Dan Shao and Outi Villet and Zhen Zhang and Choi, {Sung Won} and Jie Yan and Julia Ritterhoff and Haiwei Gu and Danijel Djukovic and Danos Christodoulou and Kolwicz, {Stephen C.} and Daniel Raftery and Rong Tian",
note = "Funding Information: We thank members of the Tian laboratory for the support. This work was supported in part by U.S. National Institutes of Health Grants HL-088634, HL-118989, and HL-129510 (to R.T.), the American Heart Association Postdoctoral Fellowship 15POST21620006 (to D.S.), the American Heart Association Scientist Development Grant 14SDG18590020 (to S.C.K.) and the Deutsche Forschungsgemeinschaft Research Fellowship 2764/1-1 (to J.R.). We thank Dr. Yibin Wang (University of California, Los Angeles) for generously providing the PP2Cm KO mice. We thank Dr. Pete Watson (University of Colorado) for his courtesy of CREB adenovirus. We thank Dr. Karol Bomsztyk (University of Washington) for providing Diagenode Bioruptor for ChIP assays. We also thank Dr. Roger J. Hajjar (Icahn School of Medicine at Mount Sinai) for providing AAV.cTnT construct. We also appreciate and thank the NHLBI Gene Therapy Resource Program and the Penn Vector Core Facility for the production of AAV9 virus. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-05362-7",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}